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Social animals expend considerable energy to maintain social bonds throughout their life. Male and female mice show sexually dimorphic behaviors, yet the underlying neural mechanisms of sociability and their dysregulation during social disconnection remain unknown. Dopaminergic neurons in dorsal raphe nucleus (DRN TH ) is known to contribute to a loneliness-like state and modulate sociability. We identified that activated subpopulations in DRN TH and nucleus accumbens shell (NAc sh ) during 24 hours of social isolation underlie the increase in isolation-induced sociability in male but not in female mice. This effect was reversed by chemogenetically and optogenetically inhibiting the DRN TH -NAc sh circuit. Moreover, synaptic connectivity among the activated neuronal ensembles in this circuit was increased, primarily in D 1 receptor–expressing neurons in NAc sh . The increase in synaptic density functionally correlated with elevated dopamine release into NAc sh . Overall, specific synaptic ensembles in DRN TH -NAc sh mediate sex differences in isolation-induced sociability, indicating that sex-dependent circuit dynamics underlie the expression of sexually dimorphic behaviors.

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Fear memory recruits various brain regions with long-lasting brain-wide subcellular events. The medial prefrontal cortex processes the emotional and cognitive functions required for adequately handling fear memory. Several studies have indicated that subdivisions within the medial prefrontal cortex, namely the prelimbic, infralimbic, and anterior cingulate cortices, may play different roles across fear memory states. Through a dedicated cytoarchitecture and connectivity, the three different regions of the medial prefrontal cortex play a specific role in maintaining and extinguishing fear memory. Furthermore, synaptic plasticity and maturation of neural circuits within the medial prefrontal cortex suggest that remote memories undergo structural and functional reorganization. Finally, recent technical advances have enabled genetic access to transiently activated neuronal ensembles within these regions, suggesting that memory trace cells in these regions may preferentially contribute to processing specific fear memory. We reviewed recently published reports and summarize the molecular, synaptic and cellular events occurring within the medial prefrontal cortex during various memory stages.